Abstract Treatment for children with cancer has progressed over the past four decades so that, today, over 80% of children diagnosed with a malignancy will become long-term survivors. Currently, there are over 350,000 survivors of childhood cancer living in the United States; nearly 250,000 of these individuals are younger than age 40 years. Unfortunately, treatment for childhood cancer continues to require agents designed to destroy malignant cell lines, and normal tissue is not always spared. While early treatment-related organ specific toxicities are not always apparent, many childhood cancer survivors report symptoms that interfere with daily life, including exercise induced shortness of breath, fatigue, and reduced capacity to participate in physical activity. These symptoms may be a hallmark of premature aging, or frailty. Frailty is a phenotype most commonly described in older adults; it indicates persons who are highly vulnerable to adverse health outcomes. Frailty may help explain why nearly two thirds of childhood cancer survivors have at least one severe chronic health condition 30 years from diagnosis, why childhood cancer survivors are more likely than peers to be hospitalized for non-obstetrical reasons, and why they have mortality rates more than eight times higher than age-and-gender matched members of the general population. The aims of this proposal are to enumerate the prevalence of physiologic frailty over time in a group of young adult survivors of childhood cancer, to describe the association between frailty and the development or progression of chronic conditions, and to describe the associations between personal factors, cancer-related treatment modalities, health behaviors, and frailty in this population.